SpringerLink
Log in

Anti-inflammatory and relaxation effects of Ulmus pumilla L. on EGF-inflamed bronchial epithelial and asthmatic bronchial smooth muscle cells

  • Original Article
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

Ulmus Pumila L. (UPL), the roots of a tree species of elm, has been prescribed for immunity-related diseases, such as dermatitis, mastitis, and edema. Despite having been prescribed for a long period of time, there are few scientific studies of UPL and asthma. Asthma, affecting 300 million people worldwide, is classified as chronic inflammation, hyperplasia, and hyper-contraction in the bronchi.

Objectives

To determine whether UPL can prevent inflammation, epidermal growth factor (EGF) in a recombinant form (10 ng/ml) was exposed to A549 cells, a type of human bronchial epithelial cell, to induce inflammation. In addition, asthmatic human bronchial smooth muscle (hBSM) cells were studied to assess the anticontraction effects of UPL.

Results

The results showed that a pretreatment with UPL, especially at the highest dosage (100 μg/ml), had significant suppressing effects on ERK/NF-κB activity compared to an EGF-only treatment group. The inhibited ERK/NF-κB activity by UPL resulted in decreased expression of cyclooxygenase (COX)-2 and its associated cytokines, in this case interleukin (IL)-4, IL-6 and TNF- α. Furthermore, the UPL treatment was determined to have anticontraction effects by regulating factors related to smooth muscle contraction, such as phospholipase C (PLC)β, inositol trisphosphate 3 receptor (IP3R) and myosin light-chain kinase (MLCK).

Conclusion

From these results, we suggest the possibility of UPL as a therapeutic agent for asthma given how it prevents inflammation and restrains bronchial smooth muscle contractions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Brazil)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

All data generated or analysed during this study are included within the article.

References

  • Abraham CM, Ownby DR, Peterson EL, Wegienka G, Zoratti EM, Keoki Williams L, Joseph CLM, Johnson CC (2007) The relationship between seroatopy and symptoms of either allergic rhinitis or asthma. J Allergy Clin Immunol 119(5):1099–1104

    Article  PubMed  Google Scholar 

  • Alam R, Gorska MM (2011) Mitogen-activated protein kinase signalling and ERK1/2 bistability in asthma. Clin Exp Allergy 41(2):149–159

    Article  CAS  PubMed  Google Scholar 

  • Amrani Y, Panettieri RA (2003) Airway smooth muscle: contraction and beyond. Int J Biochem Cell Biol 35(3):272–276

    Article  CAS  PubMed  Google Scholar 

  • Baek J-Y, Yun H-H, Im C-N, Ko J-H, Jeong SM, Lee J-H (2017) BIS overexpression does not affect the sensitivity of HEK 293T cells against apoptosis. Mol Cell Toxicol 13(1):95–103

    Article  CAS  Google Scholar 

  • Bahceciler NN, Nuhoglu Y, Nursoy MA, Kodalli N, Barlan IB, Basaran MM (2000) Inhaled corticosteroid therapy is safe in tuberculin-positive asthmatic children. Pediatr Infect Dis J 19(3):215–218

    Article  CAS  PubMed  Google Scholar 

  • Bai J, Liu XS, Xu YJ, Zhang ZX, **e M, Ni W (2007) Extracellular signal-regulated kinase activation in airway smooth muscle cell proliferation in chronic asthmatic rats. Sheng Li Xue Bao 59(3):311–318

    CAS  PubMed  Google Scholar 

  • Barnes PJ (2011) Glucocorticosteroids: current and future directions. Br J Pharmacol 163(1):29–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnes PJ, Pedersen S (1993) Efficacy and safety of inhaled corticosteroids in asthma. Report of a workshop held in Eze, France, October 1992. Am Rev Respir Dis 148(4 Pt 2):S1-26

    Article  CAS  PubMed  Google Scholar 

  • Bel EH, Zwinderman AH, Timmers MC, Dijkman JH, Sterk PJ (1991) The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease. Thorax 46(1):9–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blackwell TS, Christman JW (1997) The role of nuclear factor-κB in cytokine gene regulation. Am J Respir Cell Mol Biol 17(1):3–9

    Article  CAS  PubMed  Google Scholar 

  • Busse WW, Calhoun WF, Sedgwick JD (1993) Mechanism of airway inflammation in asthma. Am Rev Respir Dis 147(6 Pt 2):S20-24

    Article  CAS  PubMed  Google Scholar 

  • Castro-Giner F, Kauffmann F, de Cid R, Kogevinas M (2006) Gene-environment interactions in asthma. Occup Environ Med 63(11):776–786, 761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB (2010) Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med 16(11):1299–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doeing DC, Solway J (2013) Airway smooth muscle in the pathophysiology and treatment of asthma. J Appl Physiol 114(7):834–843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donahue JG, Weiss ST, Livingston JM, Goetsch MA, Greineder DK, Platt R (1997) Inhaled steroids and the risk of hospitalization for asthma. JAMA 277(11):887–891

    Article  CAS  PubMed  Google Scholar 

  • Fahy JV (2015) Type 2 inflammation in asthma—present in most, absent in many. Nat Rev Immunol 15(1):57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghasemian M, Owlia S, Owlia MB (2016) Review of anti-inflammatory herbal medicines. Adv Pharmacol Sci 2016:9130979

    PubMed  PubMed Central  Google Scholar 

  • Holgate ST (1999) Genetic and environmental interaction in allergy and asthma. J Allergy Clin Immunol 104(6):1139–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holgate ST (2008) Pathogenesis of asthma. Clin Exp Allergy 38(6):872–897

    Article  CAS  PubMed  Google Scholar 

  • In M-J, Kim DC (2016) Anti-oxidative and anti-proliferative activities of acetone extract of the cortex of Ulmus pumila L. J Appl Biol Chem 59(2):133–136

    Article  CAS  Google Scholar 

  • Jang SA, Lee SR, Koo HJ, Lee JW, Park Y, Namkoong S, Kim MK, Kang SC, Sohn EH (2017) Gamma irradiation-induced liver injury and its amelioration by red ginseng extract. Mol Cell Toxicol 13(4):461–469

    Article  CAS  Google Scholar 

  • Janssen-Heininger YM, Poynter ME, Aesif SW, Pantano C, Ather JL, Reynaert NL, Ckless K, Anathy V, van der Velden J, Irvin CG, van der Vliet A (2009) Nuclear factor kappaB, airway epithelium, and asthma: avenues for redox control. Proc Am Thorac Soc 6(3):249–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeffery PK, Wardlaw AJ, Nelson FC, Collins JV, Kay AB (1989) Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. Am Rev Respir Dis 140(6):1745–1753

    Article  CAS  PubMed  Google Scholar 

  • Jeong HY, ** S, Nam SW, Hyun SK, Kim SG, Kim BW, Kwon HJ (2014) Anti-adipogenic activity of cortex ulmi pumilae extract in 3T3-L1 preadipocytes. J Life Sci 24(2):137–147

    Article  Google Scholar 

  • Jeong JW, Hwang SJ, Han MH, Lee DS, Yoo JS, Choi IW, Cha HJ, Kim S, Kim HS, Kim GY, Jeon YJ, Lee HJ, Park HT, Yoo YH, Choi YH (2017) Fucoidan inhibits lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and zebrafish larvae. Mol Cell Toxicol 13(4):405–417

    Article  CAS  Google Scholar 

  • Keglowich L, Roth M, Philippova M, Resink T, T** G, Oliver B, Lardinois D, Dessus-Babus S, Gosens R, Hostettler Haack K, Tamm M, Borger P (2013) Bronchial smooth muscle cells of asthmatics promote angiogenesis through elevated secretion of CXC-chemokines (ENA-78, GRO-alpha, and IL-8). PLoS ONE 8(12):e81494

    Article  PubMed  PubMed Central  Google Scholar 

  • Ko J-W, Shin N-R, Park S-H, Lee I-C, Ryu J-M, Cho Y-K, Kim J-C, Seo C-S, Shin I-S (2017) Ssanghwa-Tang, a traditional herbal formula, suppresses cigarette smoke-induced airway inflammation via inhibition of MMP-9 and Erk signaling. Mol Cell Toxicol 13(3):295–304

    Article  CAS  Google Scholar 

  • Laitinen LA, Heino M, Laitinen A, Kava T, Haahtela T (1985) Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 131(4):599–606

    Article  CAS  PubMed  Google Scholar 

  • Lawrence T (2009) The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 1(6):a001651

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee JI, Burckart GJ (1998) Nuclear factor kappa B: important transcription factor and therapeutic target. J Clin Pharmacol 38(11):981–993

    Article  CAS  PubMed  Google Scholar 

  • Lee IT, Yang CM (2013) Inflammatory signalings involved in airway and pulmonary diseases. Mediat Inflamm 2013:12. https://doi.org/10.1155/2013/791231

    Article  CAS  Google Scholar 

  • Lee IS, Uh I, Kim KS, Kim KH, Park J, Kim Y, Jung JH, Jung HJ, Jang HJ (2016) Anti-inflammatory effects of ginsenoside Rg3 via NF-kappaB pathway in A549 cells and human asthmatic lung tissue. J Immunol Res 2016:7521601

    PubMed  PubMed Central  Google Scholar 

  • Lee SE, Park HR, Kim H, Choi Y, ** YH, Park CS, Ahn HJ, Cho JJ, Park YS (2017) Effect of crotonaldehyde on the induction of COX-2 expression in human endothelial cells. Mol Cell Toxicol 13(3):345–350

    Article  CAS  Google Scholar 

  • Lee IS, Cho DH, Kim KS, Kim KH, Park J, Kim Y, Jung JH, Kim K, Jung HJ, Jang HJ (2018) Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues. Immunopharmacol Immunotoxicol 40(1):83–90

    Article  CAS  PubMed  Google Scholar 

  • Li XM (2009) Complementary and alternative medicine in pediatric allergic disorders. Curr Opin Allergy Clin Immunol 9(2):161–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liggett SB (2013) Bitter taste receptors on airway smooth muscle as targets for novel bronchodilators. Expert Opin Ther Targets 17(6):721–731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu W, Liang Q, Balzar S, Wenzel S, Gorska M, Alam R (2008) Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways. The J Allergy Clin Immunol 121(4):893-902e892

    Article  CAS  PubMed  Google Scholar 

  • Maroon JC, Bost JW, Maroon A (2010) Natural anti-inflammatory agents for pain relief. Surg Neurol Int 1:80

    Article  PubMed  PubMed Central  Google Scholar 

  • Miyata M, Lee JY, Susuki-Miyata S, Wang WY, Xu H, Kai H, Kobayashi KS, Flavell RA, Li JD (2015) Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M. Nat Commun 6:6062

    Article  CAS  PubMed  Google Scholar 

  • Müller JM, Löms Ziegler-Heitbrock HW, Baeuerle PA (1993) Nuclear factor kappa B, a mediator of lipopolysaccharide effects. Immunobiology 187(3–5):233–256

    Article  PubMed  Google Scholar 

  • Nie YC, Wu H, Li PB, **e LM, Luo YL, Shen JG, Su WW (2012) Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IkappaB-NF-kappaB signaling pathways. Eur J Pharmacol 690(1–3):207–213

    Article  CAS  PubMed  Google Scholar 

  • Noble PB, Pascoe CD, Lan B, Ito S, Kistemaker LE, Tatler AL, Pera T, Brook BS, Gosens R, West AR (2014) Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling. Pulm Pharmacol Ther 29(2):96–107

    Article  CAS  PubMed  Google Scholar 

  • Ok S, Kang JS, Kim KM (2017) Cultivated wild ginseng extracts upregulate the anti-apoptosis systems in cells and mice induced by bisphenol A. Mol Cell Toxicol 13(1):73–82

    Article  CAS  Google Scholar 

  • Padmavathi P, Raghu PS, Reddy VD, Bulle S, Marthadu SB, Maturu P, Varadacharyulu NC (2018) Chronic cigarette smoking-induced oxidative/nitrosative stress in human erythrocytes and platelets. Mol Cell Toxicol 14(1):27–34

    Article  CAS  Google Scholar 

  • Pelaia G, Cuda G, Vatrella A, Gallelli L, Caraglia M, Marra M, Abbruzzese A, Caputi M, Maselli R, Costanzo FS, Marsico SA (2005) Mitogen-activated protein kinases and asthma. J Cell Physiol 202(3):642–653

    Article  CAS  PubMed  Google Scholar 

  • Perrais M, Pigny P, Copin MC, Aubert JP, Van Seuningen I (2002) Induction of MUC2 and MUC5AC mucins by factors of the epidermal growth factor (EGF) family is mediated by EGF receptor/Ras/Raf/extracellular signal-regulated kinase cascade and Sp1. J Biol Chem 277(35):32258–32267

    Article  CAS  PubMed  Google Scholar 

  • Phillips PJ, Vedig AE, Jones PL, Chapman MG, Collins M, Edwards JB, Smeaton TC, McL Duncan B (1980) Metabolic and cardiovascular side effects of the beta 2-adrenoceptor agonists salbutamol and rimiterol. Br J Clin Pharmacol 9(5):483–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salpeter SR, Ormiston TM, Salpeter EE (2004) Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest 125(6):2309–2321

    Article  CAS  PubMed  Google Scholar 

  • Sears MR, Taylor DR, Print CG, Lake DC, Li QQ, Flannery EM, Yates DM, Lucas MK, Herbison GP (1990) Regular inhaled beta-agonist treatment in bronchial asthma. Lancet 336(8728):1391–1396

    Article  CAS  PubMed  Google Scholar 

  • Sitcharungsi R, Sirivichayakul C (2013) Allergic diseases and helminth infections. Pathogens and Global Health 107(3):110–115

    Article  PubMed  PubMed Central  Google Scholar 

  • Strachan DP (2000) The role of environmental factors in asthma. Br Med Bull 56(4):865–882

    Article  CAS  PubMed  Google Scholar 

  • Tak PP, Firestein GS (2001) NF-κB: a key role in inflammatory diseases. J Clin Investig 107(1):7–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamm M, Roth M (2005) Defects of airway smooth muscle cell function are important in asthma. Swiss Med Wkly 135(41–42):607–613

    CAS  PubMed  Google Scholar 

  • Wang Y, Bai C, Li K, Adler KB, Wang X (2008) Role of airway epithelial cells in development of asthma and allergic rhinitis. Respir Med 102(7):949–955

    Article  PubMed  Google Scholar 

  • Wright D, Sharma P, Ryu MH, Risse PA, Ngo M, Maarsingh H, Koziol-White C, Jha A, Halayko AJ, West AR (2013) Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro: implications in understanding asthma. Pulm Pharmacol Ther 26(1):24–36

    Article  CAS  PubMed  Google Scholar 

  • Yatoo MI, Gopalakrishnan A, Saxena A, Parray OR, Tufani NA, Chakraborty S, Tiwari R, Dhama K, Iqbal HMN (2018) Anti-inflammatory drugs and herbs with special emphasis on herbal medicines for countering inflammatory diseases and disorders—a review. Recent Pat Inflamm Allergy Drug Discov 12(1):39–58

    Article  CAS  PubMed  Google Scholar 

  • Yoo HI, Ahn GY, Lee EJ, Kim EG, Hong SY, Park SJ, Woo RS, Baik TK, Song DY (2017) 6-Hydroxydopamine induces nuclear translocation of apoptosis inducing factor in nigral dopaminergic neurons in rat. Mol Cell Toxicol 13(3):305–315

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by a Grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant number: HF20C0030).

Author information

Author notes

  1. In-Seung Lee and Yeonjung Choi have contributed equally to this work.

Authors and Affiliations

  1. College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-Ro, Dongdaemun-Gu, Seoul, 02447, Republic of Korea

    In-Seung Lee, Wona Jee & Hyeung-** Jang

  2. Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea

    In-Seung Lee, Wona Jee & Hyeung-** Jang

  3. Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea

    Yeonjung Choi, Jihyuk Park, Hyungsuk Kim, Kwanil Kim & Hee-Jae Jung

  4. Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, 23 Kyungheedaero, Dongdaemun-Gu, Seoul, 02447, Republic of Korea

    Yeonjung Choi, Kwanil Kim & Hee-Jae Jung

Authors
  1. In-Seung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yeonjung Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wona Jee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jihyuk Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyungsuk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kwanil Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hee-Jae Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hyeung-** Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, I-SL, YC, H-JJ and H-JJ; Methodology, I-SL and YC; Investigation, I-SL and YC; Writing—original draft preparation, I-SL, YC, WJ, JP, HK, H-JJ and KK; Writing—review and editing, H-JJ. All the authors approved the manuscript.

Corresponding author

Correspondence to Hyeung-** Jang.

Ethics declarations

Conflict of interest

In-Seung Lee, Yeonjung Choi, Wona Jee, Jihyuk Park, Hyungsuk Kim, Kwanil Kim, Hee-Jae Jung and Hyeung-** Jang declare that they have no conflict of interest with the contents of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, IS., Choi, Y., Jee, W. et al. Anti-inflammatory and relaxation effects of Ulmus pumilla L. on EGF-inflamed bronchial epithelial and asthmatic bronchial smooth muscle cells. Mol. Cell. Toxicol. 20, 119–128 (2024). https://doi.org/10.1007/s13273-022-00328-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-022-00328-9

Keywords

Search

Navigation